Studies on the lipase-catalyzed resolution of amino alcohols and its application to the total synthesis of the antituberculous drug ethambutol

  • Mary Ann A. Endoma Institute of Chemistry, University of the Philippines, Quezon City
  • Susan D. Arco Institute of Chemistry, University of the Philippines, Quezon City
  • Maria Celeste R. Tria Natural Sciences Research Institute, University of the Philippines, Quezon City
Keywords: enantiomeric excess, lipase-catalyzed resolution, ethambutol, protecting groups, Mycobacterium tuberculosis

Abstract

Synthesized tosylated aminobutanol was subjected to lipase-catalyzed esterification using enzymes from different sources (Candida rugosa, porcine pancreas, and wheat germ) to screen for the lipase that gives the best resolution. It was found that C. rugosa gave the best resolved S-(+)-tosylated alcohol needed to produce (S,S)-(+)-ethambutol, the active isomer against Mycobacterium tuberculosis. However, detosylation of this compound yielded no success. Due to this, other protecting groups were used. Among those tried were t-butyloxycarbonyl (BOC) and benzyloxycarbonyl (CBZ) groups. BOC-protected alcohol failed to undergo lipase-resolution while CBZ-protected alcohol underwent smooth resolution. Deprotection ofCBZ-protected alcohol yielded the desired S-(+)-alcohol with a dismal 83% enantiomeric excess (%ee). A double resolution afforded to increase the %ee to >99%.
Published
2003-06-01
How to Cite
Endoma, M. A. A., Arco, S. D., & Tria, M. C. R. (2003). Studies on the lipase-catalyzed resolution of amino alcohols and its application to the total synthesis of the antituberculous drug ethambutol. KIMIKA, 19(1), 17-22. https://doi.org/10.26534/kimika.v19i1.17-22
Section
Research Articles